For decades, bioorthogonal reactions have pushed the frontiers of modern science. Using these selective chemistries, it is now possible to tag and retrieve bioactive metabolites directly from cells, generate libraries of complex drug molecules, and access dynamic materials for cell adhesion and patterning. The breadth of such achievements is remarkable, and as the bioorthogonal toolbox continue...

We describe the synthesis and the structural characterization of new H₂L(CF₃CO₂)₂ (1) and H₂L(Ph₂PO₄)₂ (2) compounds containing the diprotonated form (H₂L2+) of the tetrazine-based molecule 3,6-di(pyridin-4-yl)-1,2,4,5-tetrazine. X-ray diffraction (XRD) analysis of single crystals of these compounds showed that H₂L2+ displays similar binding properties toward both anions when salt bridge intera...

Detailed kinetic analyses of inverse electron-demand Diels–Alder cycloaddition and nitrilimine-alkene/alkyne 1,3-diploar cycloaddition reactions were conducted and the reactions were applied for rapid protein bioconjugation. When reacted with a tetrazine or a diaryl nitrilimine, strained alkene/alkyne entities including norbornene, trans-cyclooctene, and cyclooctyne displayed rapid kinetics. To...

The use of organic chemistry principles and prediction techniques has enabled the development of new bioorthogonal reactions. As this "toolbox" expands to include new reaction manifolds and orthogonal reaction pairings, the continued development of existing reactions remains an important objective. This is particularly important in cellular imaging, where non-specific background fluorescence ha...

Tetrazine (Tz) is an emerging bioorthogonal ligand that expected to have applications (e.g., bioimaging) in chemistry and chemical biology. In this review, we highlight the interactions of reduced tetrazine (rTz) derivatives insoluble aqueous media with biological membrane constituents or their related lipids, such as dipalmitoyl-phosphatidylcholine, dipalmitoyl-phosphatidylethanolamine, dipalm...

The additive-free tetrazine/enol ether click reaction was performed in ultra-high vacuum (UHV) with an enol group covalently linked to a silicon surface: Dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate molecules were coupled the of functionalized cyclooctyne which adsorbed on (001) surface via strained triple bond cyclooctyne. observed at substrate temperature 380 K by means X-ray photoelectron sp...

Tetrazine-functionalised boron-rich carbon dots show fast clearance and enhanced tumour accumulation under pre-targeting conditions, as demonstrated using positron emission tomography.

We present density functional theory level predictions and analysis of the basic properties of newly synthesized high-nitrogen compounds together with 3,6-bis(2H-tetrazol-5-yl)-1,2,4,5-tetrazine (BTT) and 3,3'-azobis(6-amino-1,2,4,5-tetrazine) (DAAT), for which experimental data are available. The newly synthesized high-nitrogen compounds are based on tricycle fused 1,2,4-triazine and 1,2,4,5-t...

Site-specific labeling of biomolecules is rapidly advancing due to the discovery of novel mutually orthogonal reactions. Quantum chemistry studies have also increased our understanding of their relative rates, although these have until now been based on highly simplified reactants. Here we examine a set of strain-promoted click-type cycloaddition reactions of n-propyl azide, 3-benzyl tetrazine ...